Myocardial infarction (MI) is a leading cause of death worldwide. Permanent ligation of the left anterior descending coronary artery (LAD) is a commonly used surgical model to study post-MI effects in mice. LAD occlusion induces a robust wound healing response that includes extracellular matrix (ECM) remodeling. This chapter provides a detailed guide on the surgical procedure to permanently ligate the LAD. Additionally, we describe a prototype method to enrich cardiac tissue for ECM, which allows one to focus on ECM remodeling in the left ventricle following surgically induced MI in mice. © 2013 Springer Science+Business Media New York.